Hydroxyethyl Starch Solutions: FDA Safety Communication – Boxed Warning on Increased Mortality and Severe Renal Injury and Risk of Bleeding

June 26, 2013

June 26, 2013 – The American Food and Drug Administration (FDA) has just released (June 06 2013) the following important information concerning patients who receive hydroxyethyl Starch (HES) solutions in the course of their treatment.

ISSUE: FDA has analyzed recent data that indicate an increased risk of (i) mortality and renal injury requiring renal replacement therapy in critically ill adult patients, including patients with sepsis and those admitted to the ICU; and (ii) excess bleeding particularly in patients undergoing open heart surgery in association with cardiopulmonary bypass. Refer to the FDA Safety Communication for more details about the data analysis.

FDA has concluded that HES solutions should not be used in critically ill adult patients, including patients with sepsis and those admitted to the ICU, and a Boxed Warning to include the risk of mortality and severe renal injury is warranted. In addition, FDA has reviewed a meta-analysis of studies conducted in patients undergoing open heart surgery in association with cardiopulmonary bypass and has determined that an additional warning about excessive bleeding is needed in the Warnings and Precautions Section of the package insert.

BACKGROUND: Hydroxyethyl starch (HES) solutions are used for the treatment of hypovolemia (low blood volume) when plasma volume expansion is desired. Recent data have associated the use of these products with an increased risk of severe adverse events when used in certain patient populations.

RECOMMENDATION: Patients should be aware of the risks associated with the use of HES solutions and discuss these risks with their healthcare provider (refer to the FDA Safety Communication for detailed recommendations for patients).

Recommendations for Health Professionals include the following:

– Do not use HES solutions in critically ill adult patients including those with sepsis, and those admitted to the ICU.
– Avoid use in patients with pre-existing renal dysfunction.
– Discontinue use of HES at the first sign of renal injury.
– Need for renal replacement therapy has been reported up to 90 days after HES administration. Continue to monitor renal function for at least 90 days in all patients.
– Avoid use in patients undergoing open heart surgery in association with cardiopulmonary bypass due to excess bleeding.
– Discontinue use of HES at the first sign of coagulopathy.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

Complete and submit the report Online: www.fda.gov/MedWatch/report.htm
Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
[06/24/2013 – FDA Safety Communication – FDA]


Drug Safety Communication on Brentuximab Vedotin [Adcetris] – Progressive Multifocal Leukoencephalopathy (PML) and Pulmonary Toxicity

January 17, 2012

January 16, 2012 – The American Food and Drug Administration ( FDA) released on January 13, 2012 the following drug safety communication:

_________________

ISSUE: FDA notified healthcare professionals that two additional cases of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection that can result in death, have been reported with the lymphoma drug Adcetris (brentuximab vedotin). Due to the serious nature of PML, a new Boxed Warning highlighting this risk has been added to the drug label.

In addition, a new Contraindication warning was added against use of Adcetris with the cancer drug bleomycin due to increased risk of pulmonary (lung) toxicity.

The signs and symptoms of PML may develop over the course of several weeks or months. They may include changes in mood or usual behavior, confusion, thinking problems, loss of memory, changes in vision, speech, or walking, and decreased strength or weakness on one side of the body.

BACKGROUND: Adcetris (brentuximab vedotin) is used to treat Hodgkin lymphoma and a rare lymphoma known as systemic anaplastic large cell lymphoma. At the time of Adcetris’ approval in August 2011, one case of PML was described in the Warnings and Precautions section of the label.

RECOMMENDATION: Patients who develop any signs and symptoms of PML should notify their healthcare professional immediately. Healthcare professionals should hold Adcetris dosing if PML is suspected and discontinue Adcetris if a diagnosis of PML is confirmed. See the Data Summary in the Drug Safety Communication for additional information.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

  • Complete and submit the report Online: www.fda.gov/MedWatch/report.htm1
  • Download form2 or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

 More Information as of 01/13/2012 – Drug Safety Communication3 – FDA]


Reduced Effect from Clopidogrel [Plavix] in “Poor Metabolizer” Patients

June 12, 2010

Through a new boxed warning, the FDA is alerting healthcare professionals about a subgroup of patients who cannot effectively metabolize the anti-platelet drug Clopidogrel [Plavix].

These patients, called “poor metabolizers,” have little or no activity of the liver enzyme CYP2C19, which converts Clopidogrel [Plavix] to its active form, so they may not experience the full anti-clotting benefits of the drug.

Practitioners should know that tests are available to identify genetic differences in CYP2C19 function and thus identify poor metabolizers. They should consider using other anti-platelet medication or an alternative dosing strategy for these patients. And although raising the dose of Clopidogrel [Plavix] in poor metabolizers can increase anti-platelet response, an appropriate dose regimen has not been established in a clinical trial.

Please find additional information here:

The Original Article

FDA MedWatch Safety Alert. Plavix (clopidogrel): Reduced effectiveness in patients who are poor metabolizers of the drug. March 12, 2010.

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FDA Drug Safety Communication: Reduced effectiveness of Clopidogrel [Plavix] in patients who are poor metabolizers (i.e. carriers of selected CYP2C19 allelic variants) of the drug

March 17, 2010

March 17, 2010 – The U.S. Food and Drug Administration (FDA) has added a Boxed Warning to the label for Clopidogrel [Plavix], the anti-blood clotting medication. The Boxed Warning is about patients who do not effectively metabolize the drug (i.e. “poor metabolizers”, see below) and therefore may not receive the full benefits of the drug.

The Boxed Warning in the drug label will include information to:

  • Warn about reduced effectiveness in patients who are poor metabolizers of Clopidogrel [Plavix]. Poor metabolizers do not effectively convert Clopidogrel [Plavix] to its active form in the body.
  • Inform healthcare professionals that tests are available to identify genetic differences in CYP2C19 function.
  • Advise healthcare professionals to consider use of other anti-platelet medications or alternative dosing strategies for Clopidogrel [Plavix] in patients identified as poor metabolizers.

Clopidogrel [Plavix] is given to reduce the risk of heart attack, unstable angina, stroke, and cardiovascular death in patients with cardiovascular disease. Clopidogrel [Plavix] works by decreasing the activity of blood cells called platelets, making platelets less likely to form blood clots.

For Clopidogrel [Plavix] to work, enzymes in the liver (particularly CYP2C19) must convert (metabolize) the drug to its active form. Patients who are poor metabolizers of the drug, do not effectively convert Clopidogrel [Plavix] to its active form. In these patients, Clopidogrel [Plavix] has less effect on platelets, and therefore less ability to prevent heart attack, stroke, and cardiovascular death. It is estimated that 2 to 14% of the population are poor metabolizers; the rate varies based on racial background.

Healthcare professionals should be aware that a subgroup of patients are poor metabolizers and do not metabolize Clopidogrel [Plavix] effectively; this can result in reduced effectiveness of Clopidogrel [Plavix]. Healthcare professionals should consider use of other anti-platelet medications or alternative dosing strategies for Clopidogrel [Plavix] in these patients.

Patients should not stop taking Clopidogrel [Plavix] unless told to do so by their healthcare professional. They should talk with their healthcare professional if they have any concerns about Clopidogrel [Plavix], or to find out if they should be tested for being a poor metabolizer.

In May 2009, FDA added information about poor metabolizers of Clopidogrel [Plavix] to the drug label. However, based on additional data reviewed by the agency (see Data Summary below) the Boxed Warning is now being added to highlight the reduced effectiveness of Clopidogrel [Plavix] in these patients and to recommend that healthcare professionals consider use of other anti-platelet medications or alternative dosing strategies for Clopidogrel [Plavix] in patients identified as poor metabolizers.

Additional Information for Patients and Health Care Providers Alike

Patients currently taking Plavix should:

  • Be aware that some patients do not convert Clopidogrel [Plavix] to its active form as well as other patients. These patients may not get the same benefit from Clopidogrel [Plavix]and are known as poor metabolizers.
  • Not stop taking Clopidogrel [Plavix] unless told to do so by their healthcare professional.
  • Talk with their healthcare professional if they have any concerns about Clopidogrel [Plavix].
  • Talk with their healthcare professional to see if testing to determine their metabolizer status is appropriate.

FDA recommends that healthcare professionals should:

  • Be aware that some patients may be poor metabolizers of Clopidogrel [Plavix]. They do not effectively convert Clopidogrel [Plavix] to its active form because of low CYP 2C19 activity.The effectiveness of Plavix as a preventive therapy is reduced in these patients.
  • Be aware that tests are available to determine patients’ CYP2C19 status.
  • Consider use of other anti-platelet medications or alternative dosing strategies for Clopidogrel [Plavix] in patients who have been identified as poor metabolizers.
  • Be aware that although a higher dose regimen (600 mg loading dose followed by 150 mg once daily) in poor metabolizers increases antiplatelet response, an appropriate dose regimen for poor metabolizers has not been established in a clinical outcome trial.
  • Review the newly approved Clopidogrel [Plavix] drug label for complete information on the use of Clopidogrel [Plavix].

Scientific Background and Data Summary

The liver enzyme CYP2C19 is primarily responsible for the formation of the active metabolite of Clopidogrel [Plavix]. Pharmacokinetic and antiplatelet tests of the active metabolite of Clopidogrel [Plavix] show that the drug levels and antiplatelet effects differ depending on the genotype of the CYP2C19 enzyme. The following represent the different alleles of CYP2C19 that make up a patient’s genotype:

1. The CYP2C19*1 allele has fully functional metabolism of Clopidogrel [Plavix].

2. The CYP2C19*2 and *3 alleles have no functional metabolism of Clopidogrel [Plavix]. These two alleles account for most of the reduced function alleles in patients of Caucasian (85%) and Asian (99%) descent classified as poor metabolizers.

3. The CYP2C19*4, *5, *6, *7, and *8 and other alleles may be associated with absent or reduced metabolism of Clopidogrel [Plavix], but are less frequent than the CYP2C19*2 and *3 alleles.

A patient who carries two loss-of-function alleles (as defined above) will have poor metabolizer status.

The pharmacokinetic and antiplatelet responses to Clopidogrel [Plavix] were evaluated in a crossover trial in 40 healthy subjects. Ten subjects in each of the four CYP2C19 metabolizer groups (ultrarapid, extensive, intermediate and poor) were randomized to two treatment regimens: a 300 mg loading dose followed by 75 mg per day, or a 600 mg loading dose followed by 150 mg per day, each for a total of 5 days. After a washout period, subjects were crossed over to the alternate treatment. Decreased active metabolite exposure and increased platelet aggregation were observed in the poor metabolizers compared to the other groups. When poor metabolizers received the 600 mg loading dose followed by 150 mg daily, active metabolite exposure and antiplatelet response were greater than with the 300 mg/75 mg regimen. Healthcare professionals should note that an appropriate dose regimen for patients who are poor metabolizers has not been established in clinical outcome trials.


Boxed Warning Updated: TNF Blockers and Cancer Risks in Children

November 3, 2009

November 3, 2009 – As we learn from it’s todays announcement, FDA is requiring stronger warnings about an increased risk of lymphoma and other cancers in children and adolescents who are treated with drugs that block tumor necrosis factor. TNF blockers include Infliximab [Remicade], Etanercept [Enbrel], Adalizumab [Humira], Certolizumab [Cimzia], and Golimumab [Simponi]. These drugs are used to treat juvenile rheumatoid arthritis, Crohn’s disease, and other inflammatory diseases.

The warnings, which include an updated boxed warning, are based on an FDA analysis of reports of cancer that occurred in children and adolescents treated with TNF-blockers. The cancers, some of which were fatal, occurred after an average of 30 months of treatment. About half of the cancers were lymphomas. The labeling will also include updated information on cases of leukemia and new onset psoriasis associated with TNF-blockers.

Healthcare professionals should monitor patients for development of malignancies during and after treatment with TNF blockers. They should also talk to patients and their families about this risk and tell them to report signs and symptoms of cancer such as unexplained weight loss or fatigue, easy bruising or bleeding, or swollen lymph nodes in the neck, underarms or groin.

Patients should also be monitored for signs or symptoms of new onset psoriasis or worsening psoriasis. The patient Medication Guide will be updated with this new information.

Additional Information: FDA MedWatch Safety Alert. Tumor Necrosis Factor (TNF) Blockers (marketed as Remicade, Enbrel, Humira, Cimzia, and Simponi). August 4, 2009.


FDA: Boxed Warning on Serious Mental Health Events to be Required for the Smoking Cessation Drugs Varenicline [Chantix] and Bupropion [Zyban]

July 1, 2009

July 01, 2009 – Please find here the minimally adapted text of a today’s news release by the American Food and Drug Administration (FDA) concernings drugs that contain the pharmacologically active ingredients varenicline and bupropion.

The U.S. Food and Drug Administration today announced that it is requiring manufacturers to put a Boxed Warning on the prescribing information for the smoking cessation drugs Varenicline [Chantix] and Bupropion [Zyban]. The warning will highlight the risk of serious mental health events including changes in behavior, depressed mood, hostility, and suicidal thoughts when taking these drugs.

“The risk of serious adverse events while taking these products must be weighed against the significant health benefits of quitting smoking,” said Janet Woodcock, M.D., director, the FDA’s Center for Drug Evaluation and Research. “Smoking is the leading cause of preventable disease, disability, and death in the United States and we know these products are effective aids in helping people quit.”

Similar information on mental health events will be required for Bupropion marketed as the antidepressants [Wellbutrin], [Wellbutrin SR],  [Wellbutrin XL], and for various generic versions of [Bupropion]. These drugs already carry a Boxed Warning for suicidal behavior in treating psychiatric disorders.

Woodcock said health care professionals who prescribe Chantix and Zyban should monitor their patients for any unusual changes in mood or behavior after starting these drugs. She added that patients should immediately contact their health care professional if they experience such changes.

The FDA’s request for the additional warnings is based on a review of reports submitted to the agency’s Adverse Event Reporting System since the time the products were marketed and on an analysis of information from clinical trials and scientific literature. The analyses revealed that some who have taken Chantix and Zyban have reported experiencing unusual changes in behavior, become depressed, or had their depression worsen, and had thoughts of suicide or dying. In many cases, the problems began shortly after starting the medication and ended when the medication was stopped. However, some people continued to have symptoms after stopping the medication. Also, in a few cases, the problems began after the medication was stopped.

Neither Chantix nor Zyban contain nicotine and some of these symptoms may be a response to nicotine withdrawal. People who stop smoking may experience symptoms such as depression, anxiety, irritability, restlessness, and sleep disturbances. However, some patients who were using these products experienced the reported adverse events while they were still smoking.

In addition to the Boxed Warning, the FDA also is requesting more information in the Warnings section of the prescribing information and updated information in the Medication Guide for patients that further discuss the risk of mental health events when using these products. Manufacturers also will be required to conduct a clinical trial to determine how often serious neuropsychiatric symptoms occur in patients using various smoking cessation therapies, including patients who currently have psychiatric disorders. The FDA’s review of adverse events for patients using nicotine patches did not identify a clear link between those medications and suicidal events.

_____________________

For your information, please find here, in addition to the above news release by the FDA, the text of the current Boxed Warning to be found in the drug labeling document of Bupropion [Wellbutrin]:

“Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of WELLBUTRIN or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. WELLBUTRIN is not approved for use in pediatric patients. (See WARNINGS: Clinical Worsening and Suicide Risk, PRECAUTIONS: Information for Patients, and PRECAUTIONS: Pediatric Use.)”

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Clinical Trial Data that Suggest Increased Mortality in Stable Liver Transplant Patients Receiving Sirolimus [Rapamune]

June 11, 2009

June 11, 2009 – From a today’s  MedWatch Safety Alert we learn that the American Food and Drug Administration (FDA) notified healthcare professionals of clinical trial data that suggest increased mortality in stable liver transplant 2009 06 11 Sirolimus [Rapamune] Illustration enpatients after conversion from a calcineurin inhibitor (CNI)-based immunosuppressive regimen to Sirolimus [Rapamune], which is available on all major markets worldwide (see graphic).  The trial was conducted by Sirolimus’ [Rapamune]  manufacturer, Wyeth. The Agency will continue to examine the data on mortality and other adverse events in this study, and will make further recommendations, as appropriate. The FDA is determining whether a labeling change for Sirolimus [Rapamune] is needed. In the interim, physicians should continue to use the drug’s professional labeling as a guide to therapy.

This information reflects FDA’s current analysis of data available to FDA concerning Sirolimus [Rapamune].  Posting this information does not mean that FDA has concluded there is a causal relationship between the drug product and the emerging safety issue.  Nor does it mean that FDA is advising health care professionals to discontinue prescribing this product. FDA intends to update this document when additional information or analyses become available.

Background Information: On March 25, 2009, Wyeth submitted to FDA results of a clinical trial, titled “A Randomized, Open-Label, Comparative Evaluation Of Conversion From Calcineurin Inhibitor Treatment to Sirolimus Treatment Versus Continuation Of Calcineurin Inhibitor Treatment In Liver Allograft Recipients Undergoing Maintenance Therapy”. The trial compared stable liver transplant patients who were converted from a CNI to Sirolimus [Rapamune] to patients who remained on CNI-based therapy. The trial data suggested that there may be increased mortality in patients converted from calcineurin inhibitor (CNI) therapy to Sirolimus [Rapamune]. The trial also provided additional safety and efficacy information on sirolimus:

  • The overall treatment failure rates at one year, defined as the occurrence of acute rejection or premature discontinuation for any reason, for the Intent-to-Treat population were significantly higher for the cohort of stable liver transplant patients converted to sirolimus compared to the cohort that continued on CNIs.
  • Drug discontinuation due to an adverse event was also more frequent in the Sirolimus [Rapamune] cohort compared to those patients continued on CNI.
  • Peripheral edema, stomatitis, rash, and mouth ulceration were the most frequent adverse events resulting in discontinuation in the trial.
  • Mean fasting lipid concentrations increased significantly after the Sirolimus [Rapamune] conversion, and remained elevated throughout the one year follow-up evaluation period.

At this time, FDA has not made any changes to the professional label for Sirolimus [Rapamune].  Sirolimus [Rapamune] is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving kidney transplants. The safety and the efficacy of Sirolimus [Rapamune] as an immunosuppressant have not been established in liver or lung transplant patients. This information is in the Boxed Warning of the Sirolimus [Rapamune] label.

  • The current Boxed Warning of Sirolimus [Rapamune] indicates that the use of Sirolimus [Rapamune] in combination with Tacrolimus [Prograf] was associated with excess mortality and graft loss in a study in de novo liver transplant patients.  Many of these patients had evidence of infection at or near the time of death.
  • Therapeutic drug monitoring is recommended for all patients receiving sirolimus.
  • Therapeutic drug monitoring should not be the sole basis for adjusting Sirolimus [Rapamune] therapy. Careful attention should be paid to clinical signs and symptoms, tissue biopsy findings, and laboratory parameters.
  • Patients unable to take the tablets should be prescribed the Sirolimus [Rapamune] oral solution and instructed in its use.
  • Patients should be counseled that Sirolimus [Rapamune] is to be taken by mouth, once a day, consistently and with or without food.
  • Sirolimus [Rapamune] tablets should not be crushed, chewed or split.

See the FDA Healthcare Professional Information sheet for current FDA recommendations. Adverse reactions or quality problems experienced with the use of this Product may be reported to the FDA’s MedWatch Adverse Event Reporting program either online, by regular mail or by fax, using the contact information to be found here.


FDA Requires Boxed Warning for All Botulinum Toxin Products

June 10, 2009

June 10, 2009 – From a todays’ press release by the FDA, we learn the following concerning botulinum toxin products:

Prompted by reports of serious adverse events, the American Food and Drug Administration (FDA) today announced that safety label changes, including a boxed warning, and a Risk Evaluation and Mitigation Strategy (REMS), are necessary for all botulinum toxin products.

The agency said it took the action because of reports that the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism, including unexpected loss of strength or muscle weakness, hoarseness or trouble talking, trouble saying words clearly, loss of bladder control, trouble breathing, trouble swallowing, double vision, blurred vision and drooping eyelids. These symptoms have mostly been reported in children with cerebral palsy being treated with the products for muscle spasticity, an unapproved use of the drugs. Symptoms have also been reported in adults treated both for approved and unapproved uses.

The agency also took the action because of the potential for serious risks associated with the lack of interchangeability among the three licensed botulinum toxin products.

“Updated labels for this class of products will help health care professionals and patients better understand the risks and benefits,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “Botulinum toxin products have benefits but can cause serious health problems and it is important that anyone who administers or uses these products understands these risks.”

Product Names

The products required to add the new label and a REMS are Botox and Botox Cosmetic (botulinum toxin type A), marketed by Allergan; Myobloc (botulinum toxin type B), marketed by Solstice Neurosciences; and a new FDA-approved product, Dysport (abobotulinumtoxin A), marketed by Ipsen Biopharm Ltd.

Botox, Myobloc, and Dysport are approved by the FDA for the treatment of a condition marked by repetitive contraction of the neck muscles (cervical dystonia). Botox Cosmetic and Dysport are approved by the FDA for dermatologic use in the temporary improvement in the appearance of frown lines between the eyebrows called glabellar lines. In addition, Botox is approved for the treatment of severe underarm sweating (primary axillary hyperhidrosis), crossed eyes (strabismus), and abnormal tics and twitches of the eyelids (blepharospasm).

Recommendations for Health Care Professionals

The FDA has notified the manufacturers of Botox and Myobloc that label changes and a REMS are necessary to ensure that the benefits of the product outweigh the risks. The FDA approved a REMS for Dysport as part of the product approval. The REMS for each of these products will include a Medication Guide and a Communication Plan. Medication Guides are FDA-approved handouts given to patients, or their families and caregivers, when a medicine is dispensed. The Medication Guides will contain information about the risks associated with botulinum toxin products. The FDA is also requiring the manufacturers to collect safety data in children and adults with muscle spasticity to assess the signal of risk regarding distant spread of toxin effects.

Treatment of muscle spasticity is not an FDA-approved use of botulism toxin products. The doses used in treatment of muscle spasticity are often much higher than the doses for uses described in FDA-approved product label. Symptoms consistent with spread of toxin effects have been reported at doses comparable to or lower than doses used to treat cervical dystonia. For the FDA-approved dermatologic use of temporary improvement in the appearance of glabellar lines, the agency has not identified any definitive serious adverse event reports of a distant spread of toxin effect producing symptoms consistent with botulism when the botulinum toxin products are used in accordance with the approved label.

The companies that make Botox and Myobloc are required to submit the requested safety label changes, including the boxed warning and the Medication Guide, to the FDA within 30 days, or to provide a reason why they do not believe such changes are necessary. If they do not submit new language, or the FDA disagrees with the language the companies propose, the Food, Drug, and Cosmetic Act provides strict timelines for discussions regarding the changes. At the end of these discussions the agency is allowed to issue an order directing the label change as deemed appropriate to address the new safety information.

Health care professionals who use botulinum toxins should do the following:

  • Understand that dosage strength (potency) expressed in “Units” is different among the botulinum toxin products; clinical doses expressed in units are not interchangeable from one product to another.
  • Be alert to and educate patients and caregivers about the potential for effects following administration of botulinum toxins such as: unexpected loss of strength or muscle weakness, hoarseness or trouble talking, trouble saying words clearly, loss of bladder control, trouble breathing, trouble swallowing, double vision, blurred vision and drooping eyelids.
  • Understand that these effects have been reported as early as several hours and as late as several weeks after treatment.
  • Advise patients to seek immediate medical attention if they develop any of these symptoms.

Health care professionals and consumers may report serious adverse events (side effects) or product quality problems with the use of this product to the FDA’s MedWatch Adverse Event Reporting program either online, by regular mail, fax or phone.
Online
Regular Mail: use postage-paid FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
Fax: 800-FDA-0178
Phone: 800-FDA-1088

Today’s action updates a February 2008 announcement that the FDA was conducting an ongoing safety review of botulinum toxin products.

The FDA also issued a response to a citizen petition related to the risk of spread of botulinum toxin effects from the site of injection. This response provides additional detail regarding the FDA’s analysis of this safety issue. The FDA’s response to the Citizen Petition can be found at http://www.fda.gov/cder/drug/early_comm/botulinum_CP_response.pdf

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Risk of serious fungal infections with Golimumab [Simponi]

May 31, 2009

May 31, 2009 – In a safety information to rheumatological healthcare professionals, posted May 27, 2009, FDA and Centocor Ortho Biotech remind healthcare professionals of the risk of srious fungal infections associated with Tumor Necrosis Factor – alpha (TNF-α) inhibitors, including Golimumab [Simponi].

2009 05 29 Golimumab [Simponi] Illustration enIn earlier communications, FDA has reported that histoplasmosis and other invasive fungal infections are not consistently recognized in patients taking other TNF-α inhbitors such as Certolizumab [Cimzia], Etanercept [Enbrel], Adalimumab [Humira], and Infliximab [Remicade]. This has resulted in delays in the approriate antifungal treatment of affected patients, sometimes even resulting in death. It is important that all adverse events potentially associated with Golimumab [Simponi] be reported by patients and healthcare professionals alike so that the adverse event profile reported in the prescribing information can be updated appropriately as post-approval experience is gathered.

Read the May 2009 Dear Healthcare Professional Letter sent out by Centocor here. The Prescribing Information and Medication Guide for Golimumab [Simponi] is available here. Please report any adverse event with Golimumab [Simponi] to the FDA MedWatch Program.

It should be noted here that all TNF-α inhibiting drugs mentioned herein, inclusive Golimumab [Simponi] carry in their prescribing information “Boxed Warnings” which alert to the serious riks for infections and sometimes other serious conditions (follow the links above for further details).


Tardive Dyskinesia: FDA requires Boxed Warning for Metoclopramide-Containing Drugs

May 3, 2009

May 02, 2009 – FDA is requiring that manufacturers of metoclopramide add a boxed warning to the label about the risk of tardive dyskinesia if the drug is used for long periods of time or at high doses. Metoclopramide stimulates motility in the upper GI tract and its uses include diabetic gastroparesis and gastroesophageal reflux disease.

metoclopramideMetoclopramide is marketed as a generic and under several trade names, including Reglan (see graphic to the left, generated from within ThassoBase).

Tardive dyskinesia is characterized by involuntary, repetitive movements of the extremities, as well as grimacing, rapid blinking and impaired movement of the fingers. The risk of tardive dyskinesia associated with metoclopramide is increased among long-term users of the drug, and also among elderly patients, especially women. There is no known treatment, and the symptoms, which are rarely reversible, may persist even after the metoclopramide is discontinued. However, in some patients, the symptoms may lessen or resolve when the drug is stopped.

FDA’s advice to practitioners is to avoid the chronic use of metoclopramide except in rare cases where they believe the benefit outweighs the risk. FDA is requiring manufacturers of the drug to develop a medication guide explaining the risks, which will be provided to patients with each prescription.

Please read the current announcement by the FDA here. Additional information  in an earlier announcement may be found here. A status overview  on metoclopramide-containing drug products can be found at Drugs@FDA and latest drug label information is accesible at DailyMed. Overview information on Tardive Dyskinesia is available here.


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